Diagnosis of isolated high‐grade prostatic intra‐epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re‐biopsy

Abstract

Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Multifocality, age, PSA values, and biopsy protocols regarding the predictive value of high grade PIN have been discussed extensively in the literature. Our study developed for the first time a predictive nomogram that could be helpful for patient counselling and to guide the urologist to perform rPBX after an initial diagnosis of isolated HGPIN. OBJECTIVE To evaluate factors that may predict prostate cancer (PCa) detection after the initial diagnosis of high‐grade prostatic intra‐epithelial neoplasia (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. PATIENTS AND METHODS We retrospectively evaluated 262 patients submitted from 1998 to 2007 to prostate re‐biopsy (rPBx) after an initial HGPIN diagnosis in tertiary academic centres. HGPIN diagnosis was obtained on initial systematic PBx with six to 24 random cores. All patients were re‐biopsied with a ‘saturation’ rPBx with 20–26 cores, with a median time to rPBx of 12 months. All slides were reviewed by expert uropathologists. RESULTS Plurifocal HGPIN (pHGPIN) was found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. In total, 108 and 154 patients, respectively, were submitted to >12‐core initial PBx and ≤12‐core initial PBx. Overall PCa detection at rPBx was 31.7%. PSA level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were significantly higher in patients with PCa at rPBx. PCa detection was significantly higher in patients with a ≤12‐core initial PBx than in those with a >12‐core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). At multivariable analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR, 1.09), pHGPIN (P= 0.031; HR, 1.97) and ≤12‐core initial PBx (P= 0.012; HR, 1.95) were independent predictors of PCa detection. A nomogram including these four variables achieved 72% accuracy for predicting PCa detection after an initial HGPIN diagnosis. CONCLUSIONS PCa detection on saturation rPBx after an initial diagnosis of HGPIN is significantly higher in patients with a ≤12‐core initial PBx than those with a >12‐core initial PBx and in patients with pHGPIN than in those with mHGPIN. We developed a simple prognostic tool for the prediction of PCa detection in patients with initial HGPIN diagnosis who were undergoing saturation rPBx.

Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): lack of utility to stratify cancer risks associated with HGPIN

“…Many studies have found that clinical parameters, including a patient's age, various forms of serum PSA measurement and abnormal DRE, do not correlate with the cancer risk associated with HGPIN in subsequent biopsy [5,36]. In the present study, we did not find that a patient's age and the number of repeat biopsy sessions were associated with different cancer risk.…”

“…The mean follow‐up in the present study is 27.4 months and almost half of the patients had at least two follow‐up biopsies. Longer follow‐up detects not only concomitant PCa but also new PCa that develops from HGPIN; therefore the incidence of PCa detection increases with the number of repeat biopsies and follow‐up duration [35,36]. As Lefkowitz et al .…”

Precursors of prostate cancer

“…This recommendation is based on quadrant and sextant biopsies, and may not apply for extended biopsy sampling. (Table 10) Follow‐up biopsy is suggested within one year, especially in those with multifocal PIN or those in whom PIN is detected with less than initial 12‐core biopsy 117,124,125 . If all procedures fail to identify coexistent carcinoma, close surveillance and follow‐up are indicated.…”

Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization

“…HGPIN is often found in close proximity to invasive adenocarcinomas and it shares a number of defining morphological features with invasive adenocarcinomas such as nuclear and nucleolar enlargement [11,12]. Furthermore, the presence of extensive HGPIN on prostate needle biopsy is associated with an elevated risk of cancer on subsequent biopsies [13–16]; invasive ‘microcarcinomas’ at times appear to arise from HGPIN lesions [17]; HGPIN and adenocarcinoma share a number of molecular features [11,18–20]; and HGPIN lesions share a number of somatic genetic and epigenetic alterations with invasive prostatic adenocarcinomas [4,6,11,21–27]. It is important to note, however, that most of the previous studies evaluating somatic DNA alterations in HGPIN and adjacent cancers used low-resolution and mostly fluorescence in situ hybridization (FISH)-based approaches, which although suggestive of a common clonal relationship between HGPIN and invasive carcinomas, did not allow a definitive evaluation of clonal ancestry.…”